The early onset forms of periodontal disease, including juvenile (JP) and rapidly progressive (RP) periodontitis, represent a major health concern. Although these disorders have been recognized for many years, and their familial nature implicated, systematic investigation of clinical manifestations and laboratory diagnostic tests have only recently been initiated. The pathogenesis of early onset periodontitis is not yet understood, and carefully designed comprehensive family studies provide the most promising approach to elucidating underlying cellular and biochemical correlates of JP and RP, as well as permitting investigation into the mode(s) of inheritance and variability of the phenotypes. The goal of the proposed research is to assemble the largest group of JP and RP patients currently available, and to perform systematic and comprehensive clinical evaluations of probands and all available first-degree relatives. Neutrophil chemotaxis assays will be performed, and blood samples, collected for linkage studies, will be analyzed in collaboration with other Clinical Research Centers for Periodontal Diseases. Formal pedigree analysis will be performed to test Mendelian hypotheses, and to estimate segregation ratios or transmission probabilities. Inheritance patterns will be studied for both laboratory parameters and clinical phenotypes, taking into account complicating factors including age, age of onset, and indeterminate diagnostic categories. Simulation studies will be performed to assess the importance of missing paternal data, and sex and age factors as complications in the interpretation of the segregation analyses. Within and among family variability will be investigated, and correlations between laboratory findings and clinical manifestation determined. The results of these family studies will provide: (1) insight into potential methods of presymptomatic or early diagnosis; (2) clarification of the variability of these diseases and diagnostic categorization; (3) the determination of risk to relatives of probands; and (4) a nucleus for larger studies of etiologic mechanisms and genetic heterogeneity among the forms of early onset periodontitis.